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Query: UNIPROT:P06889 (Mol)
 630,302 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In the accompanying paper (Friedman et al., Mol. Cell. Biol. 6:3791-3797, 1986), hepatoma-specific expression of the rat albumin promoter within the adenovirus genome was demonstrated. However, the rate of transcription was very low compared with that of the endogenous chromosomal albumin gene. Here we show that in hepatoma cells the adenovirus E1A enhancer, especially in the presence of E1A protein, greatly stimulates transcription from the albumin promoter but not the mouse beta-globin promoter. This enhancer-dependent stimulation did not occur in myeloma cells in which a virus containing a immunoglobulin promoter and enhancer did function. These experiments suggest a limited distribution in cultured differentiated cells of cell-specific transcription factors. However, either the regulation of such cell-specific factors breaks down in other cultured cells, or strictly cell-specific factors are not at play in controlling cell-specific transcription, because HeLa cells could transcribe the albumin promoter from the same start site about 10% as well as hepatomas could and 293 cells could transcribe both albumin and globin promoters.
Mol Cell Biol 1986 Nov
PMID:Cellular promoters incorporated into the adenovirus genome: effects of viral regulatory elements on transcription rates and cell specificity of albumin and beta-globin promoters. 294 9

We examined the ability of U1 small nuclear ribonucleoproteins (U1 snRNPs) to recognize mutant and cryptic 5' splice sites on beta-globin pre-mRNA substrates using an RNase T1 protection assay. When U1 snRNPs were prebound to anti-(U1)RNP antibodies, we detected binding to mutant but not to cryptic 5' splice sites on several substrates. By contrast, in a splicing extract at 0 degree C, neither the mutated nor cryptic 5' splice sites of a human beta-globin transcript were selected as protected fragments with the same antibodies. However, after incubation of the transcript in the extract to yield splicing intermediates, fragments that included a cryptic 5' splice site were detected. The results of our analyses suggest that U1 snRNPs are involved in recognizing cryptic 5' splice sites but that interactions with other splicing components are required to stabilize the association.
Mol Cell Biol 1987 Feb
PMID:Recognition of mutant and cryptic 5' splice sites by the U1 small nuclear ribonucleoprotein in vitro. 295 Mar 13

Protection experiments with antibodies against small nuclear ribonucleoproteins (snRNPs) have elucidated the location of and requirements for interactions between snRNPs and human beta-globin transcripts during splicing in vitro. U2 snRNP association with the intron branch site continues after branch formation, requires intact U2 RNA, and is affected by some alterations of the 3' splice site sequence. U2 snRNP binding to the branched intermediate and U1 snRNP protection of an extended 5' splice region are detected exclusively in spliceosome fractions, indicating that both snRNPs are spliceosome components. While each snRNP associates specifically with the pre-mRNA, they also appear to interact with each other. The recovery of fragments mapping upstream of the 5' splice site suggests how the excised exon is held in the spliceosome.
Mol Cell Biol 1987 Jan
PMID:Multiple interactions between the splicing substrate and small nuclear ribonucleoproteins in spliceosomes. 295 86

The synthesis of globin protein in blood reticulocytes of patients from Tajikistan suffering from homozygous beta-thalassemia was studied. Beta-thalassemia has been revealed in all cases, with synthesis of beta-globin being retained though essentially reduced. It was shown that, unlike homozygous beta+-thalassemia of other populations, beta +thalassemia with sharp inhibition of the beta-globin protein synthesis is most representative for the region (alpha/beta greater than 10).
Mol Gen Mikrobiol Virusol 1987 Aug
PMID:[Characteristics of the expression of globin genes in blood cells of patients with homozygotic beta-thalassemia from Tadzhikistan]. 296 Aug 92

The synthesis of globin proteins in blood reticulocytes of homozygous beta-thalassemic patients from Tadzhikistan has been previously studied. beta-thalassemia with sharp repression of beta-globin protein synthesis (alpha/beta greater than 10) has been shown to be most representative for the region. In this work, the synthesis of globin proteins has been studied in bone marrow cells of homozygous beta-thalassemic patients. Comparison of data on globin synthesis in bone marrow cells and in blood reticulocytes of the patients has revealed that in some cases the disbalance of chain synthesis in both cell types is equal. In other cases the disbalance in bone marrow cells is less than in blood cells, indicating the instability of beta-globin mRNA that is partially degrading in the process of cell maturation. Homozygous beta-thalassemic cases with low content of Hb F in blood cells (5-10%), with substantial disbalance of alpha and beta-globin synthesis and marked production of gamma-globins in bone marrow cells and in blood reticulocytes are of special interest. It has been assumed that parallel to beta-thalassemia some instability of gamma-globin proteins takes place in these patients.
Mol Gen Mikrobiol Virusol 1988 Oct
PMID:[Heterogeneity of globin protein synthesis in bone marrow cells of patients with homozygous beta-thalassemia from Tadzhikistan]. 297 80

We used several quantitative assays of in vivo transient gene expression to dissect the elements within the Rous sarcoma virus long terminal repeat (LTR) which constitute the retroviral transcription control region. Site-directed deletion mutagenesis was used to locate and define the enhancer and promoter elements within the LTR. In addition, we inserted exogenous DNA fragments into the LTR to examine the effects of position and sequence on the activity of these LTR transcriptional elements. The Rous sarcoma virus enhancer element, which we propose is located entirely within the LTR, was shown to activate both the beta-globin and retroviral LTR promoters when located in cis. We observed a striking correlation between the degree of activation and the distance between the retroviral promoter and enhancer elements. The LTR promoter element mediated the activation effect of the enhancer element, as LTR deletion mutants containing only the enhancer and TATA box region expressed little activity. The promoter region encoded a low but significant level of transcriptional activity even in the absence of an enhancer. Overall LTR transcriptional activity declined sharply with increasing distance between the LTR promoter and initiator elements. These results shed light on both the importance of the spatial arrangement of the sequence elements within this eucaryotic transcription control region and on the functional interrelationship between these elements.
Mol Cell Biol 1985 Mar
PMID:Functional analysis of the transcription control region located within the avian retroviral long terminal repeat. 298 53

Sequences that comprise the 244-base-pair polyomavirus enhancer region are also required in cis for viral DNA replication (Tyndall et al., Nucleic Acids Res. 9:6231-6250, 1981). We have studied the relationship between the sequences that activate replication and those that enhance transcription in two ways. One approach, recently described by de Villiers et al. (Nature [London], 312:242-246, 1984), in which the polyomavirus enhancer region was replaced with other viral or cellular transcriptional enhancers suggested that an enhancer function is required for polyomavirus DNA replication. The other approach, described in this paper, was to analyze a series of deletion mutants that functionally dissect the enhancer region and enabled us to localize four sequence elements in this region that are involved in the activation of replication. These elements, which have little sequence homology, are functionally redundant. Element A (nucleotides 5108 through 5130) was synthesized as a 26-mer with XhoI sticky ends, and one or more copies were introduced into a plasmid containing the origin of replication, but lacking the enhancer region. Whereas one copy of the 26-mer activated replication only to 2 to 5% of the wild-type level, two copies inserted in either orientation completely restored replication. We found that multiple copies of the 26-mer were also active as a transcriptional enhancer by measuring the beta-globin mRNA levels expressed from a plasmid that contained either the polyomavirus enhancer or one or more copies of the 26-mer inserted in a site 3' to the beta-globin gene. We observed a correlation between the number of inserted 26-mers and the level of beta-globin RNA expression.
Mol Cell Biol 1985 Apr
PMID:Polyomavirus enhancer contains multiple redundant sequence elements that activate both DNA replication and gene expression. 298 64

Transient expression of an SV40-based shuttle vector similar in design to commonly used vectors is shown to be inefficient when compared to expression of SV40 viral DNA. To eliminate this problem, we have designed and constructed a new vector, pSVPiC, which contains a minimal noninterfering plasmid component, the 885-bp plasmid PiAN7, and two SV40 promoter/origin regions. Transient expression of the SV40 late region from pSVPiC is much more efficient than that from previously used vectors and even more efficient than that from SV40 viral DNA. When the gene for rabbit beta-globin is placed in the late region of pSVPiC, it is also expressed at high levels, indicating that this shuttle vector is generally useful for expressing eukaryotic genes.
J Mol Appl Genet 1985
PMID:Comparison of the transient late region expression of SV40 DNA and SV40-based shuttle vectors: development of a new shuttle vector that is efficiently expressed. 298 6

We have studied the extrachromosomal maintenance and the transcription regulation of two glucocorticoid-inducible genes on bovine papilloma virus (BPV) vectors in c127 mouse fibroblasts. These genetic elements were the rat tryptophan oxygenase (TOase) gene promoter, which is active in vivo only in hepatocytes, and the long terminal repeat of the mouse mammary tumor virus (MMTV-LTR). From both genes, fusions of the 5'-flanking region of the transcription unit to the bacterial gene for chloramphenicol acetyltransferase (CATase) were constructed. These fusion genes were inserted either into pCGBPV9, a BPV vector encoding G418 resistance, into pBPV-BV1, a vector containing "stabilizing" segments of the human beta-globin gene, or into a BPV construct, whose bacterial plasmid sequences could be removed before transfection. Five constructs of the two latter groups, selectable in c127 cells only as foci, were normally maintained in the extrachromosomal state. In contrast, three out of five constructs based on pCGBPV9 and selectable for resistance against G418 were maintained in a high molecular weight form, most probably of intrachromosomal concatemeric nature, while the remaining two G418-resistant constructs appeared alternatively in this or the extrachromosomal monomeric form. In contrast to its absence of expression in fibroblasts in vivo, the TOase gene element present on BPV vectors was found to be active in fibroblasts in these transfection experiments. As judged by CATase activities and for TOase also by mapping of the transcription start sites, transcription of both genes was under hormonal regulation. All BPV vectors proved to be useful tools in the study of these regulated genes, and in only one out of ten constructs was regulation atypical, possibly due to effects from flanking vector sequences.
J Mol Biol 1986 Feb 20
PMID:Physical state, expression and regulation of two glucocorticoid-controlled genes on bovine papilloma virus vectors. 301 94

The herpes simplex virus type 1 thymidine kinase (tk) gene lacks introns and produces stable mRNA in the absence of splicing. We have prepared a hybrid gene by placing the first exon, first intron (first intervening sequence, designated IVS1), and most of the second exon of the normal human beta-globin gene into the 3' untranslated region of the tk gene. Although this hybrid gene contains all globin sequences presumed necessary for the splicing of IVS1, predominantly, unspliced stable cytoplasmic RNA is produced in both long- and short-term expression assays. Moreover, stable unspliced cytoplasmic RNA is detected whether the intron is situated in a sense or an antisense orientation. Efficient splicing of IVS1 is obtained either by deleting the majority of tk coding sequences or by relocating the globin sequences from the 3' to the 5' untranslated region of the tk gene.
Mol Cell Biol 1985 Aug
PMID:Synthesis of predominantly unspliced cytoplasmic RNAs by chimeric herpes simplex virus type 1 thymidine kinase-human beta-globin genes. 301 35


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